The major objective of this research proposal is to define the roles of glucose, insulin and gastric inhibitory polypeptide in the regulation of adipose tissue lipoprotein lipase. Previous studies have shown the ability to distinguish between synthesis, potential for secretion and secretion of the enzyme. This model of adipose tissue lipoprotein lipase regulation can then be applied to both in vivo and in vitro investigations. Studies of glucose, insulin and gastric inhibitory polypeptide control of lipoprotein lipase in cell culture will be performed in 3T3-L1 cells, a fibroblast cell line already utilized by the principal investigator for studies of enzyme regulation. In these cells, the ability to study specific mechanisms of glucose or hormone action can be performed by selective inhibition of either lipoprotein lipase synthesis or secretion. In vivo investigations will be carried out by use of the glucose clamp technique. Baseline and sequential adipose tissue biopsies for measurement of lipoprotein lipase will be performed in normal weight controls, obese controls and maturity-onset diabetics. Studies planned will investigate the independent control of adipose tissue lipoprotein lipase activity by glucose and insulin in both controls and diabetics. The role of gastric inhibitory polypeptide in enzyme control will be examined in normal weight controls at normal and elevated plasma glucose concentrations. A synergistic interaction of insulin and gastric inhibitory polypeptide in the regulation of adipose tissue lipoprotein lipase will also be tested. While studies to demonstrate the aplicability of the 3T3-L1 cell model to human adipose tissue lipoprotein lipase are ongoing, attempts to establish a cultured human preadipocyte system for future study of adipose tissue lipoprotein lipase will continue. It is expected that the studies proposed will provide information and test hypotheses which should help elucidate the role of glucose, insulin and gastric inhibitory polypeptide in regulation of adipose tissue lipoprotein lipase. This will not only further our understanding of physiologic control mechanisms, but allow the ability to correct defects in adipose tissue lipo-protein lipase found in human disease such as insulin deficient diabetes mellitus.